The major goal of this Phase I proposal is to develop a robust in vitro 3D system that reflects cellular tumor heterogeneity and recreates the tumor microenvironment in vivo, the lack of which has severely limited prediction of clinical efficacy of a drug(s). A 3D system that could better guide decision making on clinical efficacy of drugs remains an unmet need. To this end, a team of multidisciplinary scientists at Transgenex Nanobiotech Inc. and the University of South Florida, has recently developed an electrospun random fiberinspired smart scaffold (FiSS), on which tumor biopsy-derived cells form tumoroids, tumor-like structures (BdT). Resemblance of tumoroids to in vivo tumors in epithelial-mesenchymal transition (EMT) and drug sensitivity has led to the hypothesis that FiSS-BdT platform can be used to develop personalized cancer therapy (PCT). To test this hypothesis in Phase I, it is planned to compare the BdTs with xenografted tumors of human lung cancer cell lines with respect to EMT, cellular heterogeneity and stem cell content; and demonstrate accurate prediction of clinical efficacy of the BdT platform using prototypical cancer drugs. These results will set the stage for the validation of a robust BdT assay for PCT and new-device enabling Phase II application.